1. Field of the Invention
The present invention relates to strip-shaped forms of administration, or administration forms, for administering an active ingredient via the mucous membrane of the gums.
2. Description of the Prior Art
Strip-shaped products for application in the mouth are sold in the cosmetic field as dental care products. There are, for example, tooth-whitening strips available on the market that are provided with a tooth-bleaching composition and are placed on the teeth to achieve a long-lasting contact between the teeth and the bleaching composition. Such tooth-whitening strips are described, for example, in the patent specifications U.S. Pat. No. 5,879,691, U.S. Pat. No. 6,045,811 and U.S. Pat. No. 6,136,297, as well as in the published application US 2006/0292520 A1.
Strip-shaped products for oral administration of active pharmaceutical ingredients are available in the form of forms of administration that disintegrate in the mouth. These strip-shaped forms of administration are usually designated as “thin oral strips” or “wafers”. Products of this type that are already being marketed are the products soled under the trade marks TRIAMINIC®, THERAFLU®, GAS-X® or BENADRYL®, for example. These products are pharmaceutical preparations that are designed such that the form of administration quickly disintegrates in the mouth. Their rapid disintegration is meant to facilitate swallowing the active pharmaceutical ingredient contained therein. After swallowing, the active pharmaceutical ingredient is absorbed in the gastrointestinal tract. The active pharmaceutical ingredient administered with these commercially available strip-shaped forms of administration is therefore subject to the “first pass” metabolism.
One possibility of avoiding the “first pass” metabolism is the absorption of active pharmaceutical ingredients directly via the mucous membranes. The blood circulation through the mucous membranes takes place via a network of capillaries that allow direct access of the active ingredient to the systemic blood circulation. It is thereby possible to avoid the “first pass” metabolism by diffusion of an active ingredient into the capillary network of the oral mucosa. To achieve this, the active ingredient must be prevented from being swallowed prematurely and its absorption in the oral cavity via the mucous membrane has to be enhanced.
The lips, the cheeks, the hard and the soft palate, the tongue and the floor of the mouth define the oral cavity. Since the mucous membranes of the oral cavity are readily accessible, the oral cavity is a site especially suited for a transmucosal administration of active ingredients. The oral mucous membranes include the sublingual mucosa, the buccal mucous membranes, the mucosa of the gums, the mucous membranes of the palates, as well as the mucous membranes of the lips. The specific site of application in the oral cavity can have an effect on the bioavailability of an active ingredient. In the oral cavity, the transmucosal absorption of active ingredients predominantly takes place via the non-keratinised mucous membranes, above all in the region of the cheeks and below the tongue. However, active ingredients can also be absorbed via the keratinised tissue of the gums. Choosing the gums as the application site affords three major advantages: (A) a very strong blood circulation, so that there is a good access to the systemic blood circulation, (B) a low mechanical stress acting on a form of administration applied there, e.g. chewing movements, (C) only little saliva flowing around the form of administration so that a reduced portion of active pharmaceutical ingredient is swallowed.
An important factor influencing the bioavailability is the contact time between the absorptive epithelial tissue and the active pharmaceutical substance. In principle, a partial absorption can also take place in a rapidly disintegrating form of administration, it is true, but only on condition that the active ingredient has favourable physicochemical properties in terms of transmucosal absorption, e.g. low molecular weight, lipophilic character, etc. For the majority of the active ingredients, particularly peptide agents, for which a transmucosal administration would be advantageous, a prolonged contact time with the absorptive mucous membrane surface is of crucial importance to enable the active ingredient to be absorbed in an amount necessary for achieving the therapeutic effect.
What is available on the market for administering active ingredients via the oral mucous membranes, besides spraying solutions, are above all various tablet formulations. There are sublingual tablets, e.g. NICORETTE® microtabs, which contain nicotine, or UPRIMA® tablets, which contain apomorphine as active ingredient. In addition, there are buccal tablets, e.g. FENTORA®, which contain fentanyl, or BUCCASTEM®, which contain prochlorperazine as active ingredient. Such tablets, however, do have some disadvantages, including (A) an unpleasant mouthfeel, since they cause a sensation of having a foreign body under the tongue, (B) variability in the extent of absorption, and (C) the risk of a complete tablet being swallowed cannot be excluded.
To avoid or at least ameliorate these disadvantages, it would be desirable to have a dosage form by which an active ingredient can be reliably administered via a mucous membrane in the oral cavity, the dosage form being applied at a site in the mouth that does not encumber the patient and where it can be worn even for a prolonged period of time. In addition, it would be advantageous if the dosage form were adapted such that only a correct positioning, and one that is self-explanatory to the user, will be possible in order to avoid application errors.